Hepatic Arterial Resistance Research Articles

THE ROLE OF β‐ADRENOCEPTORS IN THE RESPONSES OF THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG TO PHENYLEPHRINE, ISOPRENALINE, NORADRENALINE AND ADRENALINE

The sympathetically‐innervated hepatic arterial vascular bed of the dog was perfused from a femoral artery. Hepatic arterial blood flow and perfusion pressure were recorded continuously, and the hepatic arterial vascular resistance (HAVR) calculated from these measurements. Intra‐arterial injections of phenylephrine caused dose‐dependent rises in HAVR, indicating hepatic arterial vasoconstriction, at all doses above threshold. No secondary reductions in HAVR followed these responses. Intra‐arterial injections of isoprenaline caused only dose‐dependent reductions in HAVR at doses above threshold. Intra‐arterial injections of noradrenaline typically caused an initial increase in HAVR which was followed at all but the highest doses by a secondary, delayed, reduction in HAVR. Intra‐arterial injections of adrenaline, like those of noradrenaline, resulted in hepatic arterial vasoconstriction followed by hepatic arterial vasodilatation. On a molar basis, the most potent hepatic arterial vasoconstrictor was noradrenaline, followed by adrenaline and phenylephrine. The maximum reductions in HAVR caused by adrenaline (mean reduction = 21.9%) and noradrenaline (16.9%) were significantly smaller than those due to isoprenaline (P < 0.001). Propranolol attenuated the hepatic arterial vasodilator responses due to isoprenaline, and the secondary falls in HAVR following intra‐arterial adrenaline and noradrenaline. Propranolol did not modify the vasoconstrictor responses to phenylephrine. Both adrenaline and noradrenaline were more potent hepatic arterial vasoconstrictors after propranolol than in the absence of β‐adrenoceptor blockade. The potentiation of the vasoconstrictor effects of adrenaline was statistically significant. After propranolol, adrenaline was a more potent hepatic arterial vasoconstrictor than noradrenaline. Since the β‐adrenoceptors in the hepatic arterial vasculature were not blocked by atenolol, but were stimulated by salbutamol, it is concluded that they are predominantly of the β2‐type. The vasoconstrictor actions of phenylephrine, noradrenaline and adrenaline were all antagonized by the systemic administration of phentolamine, all three dose‐response curves being shifted to the right. The results are discussed with regard to the possible control of the hepatic arterial vasculature by naturally‐occurring catecholamines.

The effects of glucagon, secretin, pancreozymin and pentagastrin on the hepatic arterial vascular bed of the dog.

1 The sympathetically-innervated arterial vascular bed of the dog's liver was perfused from a femoral artery. Arterial blood flow and perfusion pressure were monitored continuously and the hepatic arterial vascular resistance (HAVR) calculated from these measurements. 2 Commercial preparations of secretin, pancroezymin, glucagon and pentagastrin were administered by intra-arterial (i.a.) injection and infusion. 3 Secretin and pancreozymin by injection caused dose-dependent hepatic arterial vasodilatation, and on a molar basis were both more potent than glucagon or pentagastrin. 4 Intra-arterial infusions of secretin and pancreozymin caused hepatic arterial vasodilatation at calculated blood concentrations close to those measured under physiological conditions by other investigators. The vasodilatation was of the same duration as that of the hormone infusions. 5 Pentagastrin by i.a. injection caused dose-dependent hepatic arterial vasodilatation; by i.a. infusion, vasodilatation occurred but there was marked 'escape' from the effects during the continued infusion. 6 As reported previously, glucagon by injection caused dose-dependent hepatic arterial vasodilatation of long duration; by infusion, glucagon caused vasodilatation that persisted after the cessation of the infusion. 7 Glucagon infused i.a. inhibited the vasoconstricter effects of i.a. noradrenaline, over the same range of infusions that caused hepatic arterial vasodilatation. 8 Secretin or pancreozymin did not antagonize the effects of noradrenaline on the hepatic arterial vascular bed at any doses used. 9 Pentagastrin did not antagonize the vasoconstrictor effect of noradrenaline whether hepatic arterial vasodilatation resulted from the pentagastrin infusion, or not. 10 These results are discussed with respect to the possible control of the hepatic arterial vascular bed by gastrointestinal hormones.

THE VASODILATOR ACTIONS OF ISOPRENALINE, HISTAMINE, PROSTAGLANDIN E2, GLUCAGON AND SECRETIN ON THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG

The sympathetically-innervated arterial vascular bed of the dog's liver was perfused from a femoral artery. Arterial blood flow and perfusion pressure were measured continuously, and the hepatic arterial vascular resistance calculated. The preparation provided a means of assessing hepatic arterial vasodilatation quantitatively. 2 Isoprenaline, histamine, prostaglandin E2, glucagon and secretin were injected intra-arterially and all evoked dose-dependent vasodilatation of the hepatic arterial vascular bed. 3 The maximum reduction in the calculated hepatic arterial vascular resistance of 37-38% was the same for each of the five substances. 4 Comparisons on a weight basis revealed that prostaglandin E2 was the most potent, followed in potency order by secretin, isoprenaline, histamine and glucagon. 5 Comparisons on a molar basis showed that secretin and prostaglandin E3 were intrinsically considerably more potent than isoprenaline, histamine or glucagon. 6 The onset of the vasodilatator responses to secretin, isoprenaline, histamine and prostaglandin E2, was rapid, and the duration of their actions was brief. 7 The onset of the vasodilator effects of glucagon was slow and its duration of action very prolonged. 8 The implications of these observations with respect to the physiological control of the hepatic arterial vascular bed of the dog are discussed.

The inhibition by glucagon of the vasoconstrictor actions of noradrenaline, angiotensin and vasopressin on the hepatic arterial vascular bed of the dog.

1 The hepatic artery of the anaesthetized dog was cannulated and perfused from a femoral artery, the blood flow and perfusion pressure being monitored continuously. The sympathetic periarterial nerves were divided. 2 Dose-dependent increases in hepatic arterial vascular resistance (HAVR) resulted from intra-arterial injections of noradrenaline, angiotensin and vasopressin. 3 Single injections of glucagon (100 mug, i.a.) caused a transient significant fall in HAVR of 19.9 +/- 3.2%, and infusions of 25 mug/min of glucagon intra-arterially caused maintained reductions in HAVR of 16.9 +/- 4.2%. 4 After single injections of 100 mug glucagon intra-arterially the vasoconstrictor responses to noradrenaline, angiotensin, and vasopressin were reduced by about 85-95%. Recovery occurred in 8-10 minutes. 5 Intra-arterial infusions of glucagon, 2.5-50.0 mug/min, reduced the effects of test doses of noradrenaline, angiotensin and vasopressin throughout the period of the infusions. 6 Dose-response curves to the constrictor agents were constructed before, during and after intra-arterial infusions of 25 mug/min of glucagon. Glucagon caused a parallel shift of the curves for noradrenaline and angiotensin to the right, with no suppression of the maximum response. 7 Infusions of glucagon shifted the dose-response curve for vasopressin to the right, but, in contrast to noradrenaline and angiotensin, the shift was nonparallel and there was a suppression of the maximum response by about one-half. 8 A large dose of insulin, 10 iu, transiently reduced HAVR and caused a weak and very transient inhibition of the effect of test doses of noradrenaline. The characteristics of these effects were quite different from those of glucagon. 9 It is possible that the antagonism by glucagon of the vasoconstrictor responses of the hepatic arterial vasculature may be important in protecting this vascular bed from the effects of concomitantly released vasoconstrictor agents.

FACTORS PRODUCING VARIOUS RESPONSES TO ACETYLCHOLINE IN DOG HEPATIC CIRCULATION

Effect of acetylcholine on hepatic circulation was investigated in 33 mongrel dogs. Mean arterial blood pressure, hepatic artery flow, portal vein pressure and portal vein flow were determined after laparotomy under nembutal anesthesia. In order to analyse the complicated responses in hepatic blood flows to 3 μg of acetylcholine hydrochloride, the peripheral resistance of each vascular system was observed in hypotensive dogs, in vascular obliteration dogs and in portal vein shunting dogs. Observation under a hypotensive condition produced by exsanguination revealed that hepatic artery resistance responded to decrease in hepatic artery pressure in different ways depending on whether the systemic blood pressure was above or below 90 mmHg. Experiments in which the hepatic artery or portal vein were obliterated disclosed that there was a certain regularity in the induction of resistance change in the non-injected one of the two hepatic vessels. The result of shunting the portal vein suggested that the complicated change above mentioned would be the expression of the overlapping two sequential responses. Since these results are difficult to explain merely by the direct response of vascular smooth muscle to acetycholine, the possibility that the hypothetical communication between the hepatic artery and portal vein might be a cholinergic system was discussed.

Effect of controlled halothane anaesthesia on splanchnic blood flow and cardiac output in the dog.

Effects of halothane anaesthesia on aplanchnic blood flow and cardiac output were studied in six dogs. Blood flows in the hepatic artery, the superior mesenteric artery and the portal vein were measured electromagnetically. Cardiac output was measured by thermodilution. Depth of anaesthesia, ventilation, acid-base state and body temperature were controlled. Cardiac output and blood flows in the hepatic artery, the superior mesenteric artery and the portal vein decreased significantly to 73%, 54%, 59% and 60% of control values, respectively. Total peripheral vascular resistance decreased significantly, while mesenteric and portal resistance remained essentially unchanged and hepatic arterial resistance showed a significant increase. It is suggested that the difference between the various vascular responses may be caused by a differentiated release from baroreceptor inhibition in various parts of the bulbar vasomotor center.

Hepatic circulation in acute hemorrhage with reference to renal circulation.

Studies were made on the hemodynamics in the liver and kidney during hemorrhage and retransfusion, using 20 dogs with or without hepatic periarterial nerve plexus, anaesthetized with sodium pentobarbital. The results were as follows. In 14 dogs in which the hepatic periarterial nerve plexus was left intact (Group A), the averages of the hepatic arterial flow (HAF), portal venous pressure (PVP), portal venous flow (PVF), and flow in the right renal artery (RAF) decreased significantly to 38, 64, 35, and 25%, respectively of the control levels when the abdominal aortic pressure (ABP) fell to 40 mm Hg (36% of the control level) during hemorrhage. At the same time the portal venous resistance (PVR) and the right renal vascular resistance (RVR) increased greatly and the hepatic arterial resistance (HAR) either increased or decreased in different dogs. During retransfusion the ABP and vascular resistance returned to nearly the control levels, the PVF increased beyond the control level. In 6 dogs in which the nerve plexus was resected (Group B), the decreases in the HAF and RAF during hemorrhage were not significantly different from those in Group A. These results may suggest the following. The decrease in the HAF during hemorrhage seems to be mostly a passive change resulting from decrease in the systemic blood pressure. Neurogenic regulation may be a little. Further, the existence of the humoral regulation and autoregulation in the HAF were suggested in some cases. While, the responsibilities to hemorrhage and retransfusion appear to be different among the examined three vessels, i.e. the hepatic artery, portal vein, and renal artery. No definite interrelation was seen between the hepatic and renal circulations.

Hemodynamic effects of CCl4 in the intact liver of the cat.

Blood flow in the intact liver of anesthetized cats did not change significantly over a period of 4 h following intraduodenal injection of CCl4 (1 ml/kg). Hepatocellular disruption was well underway by 2 h after the injection. Twenty-four hours following an oral dose of CCl4, the hepatic arterial resistance to blood flow was reduced and total blood flow to the liver was at least as high as in control animals. At this time, the hepatic artery appeared fully dilated and was less responsive to humoral (intra-arterial infusion of noradrenaline) and neural (reflex activation of the sympathetic nerves) constrictor influences. Thus, alterations in hepatic blood flow do not occur during the early phases of CCl4-induced hepatic injury. These data indicate that diminished blood flow is not a causative factor in the initial phases of CCl4-induced liver injury. By 24 h, hepatic blood flow is altered in such a manner that the damaged liver receives a higher proportion of arterial blood and a total blood flow that is not reduced in spite of a generally depressed cardiovascular system.

The effect of hemorrhage on hepatosplanchnic hemodynamics, liver function and hepatic metabolism.

AbstractKrarup, N. The effect of hemorrhage on hepatosplanchnic hemodynamics, liver function and hepatic metabolism. Acta physiol. scand. 1973. 89. 269–277.Cats in the postabsoiptive state and anesthetized with chloralose were used for the experiments. Following a control period the cats were bled approximately 25 % of the blood volume. The total liver blood flow decreased in parallel to the mean arterial blood pressure, due to a large decrease in portal flow, whereas the hepatic arterial flow remained constant. Thus the splanchnic vascular resistance was not changed, the hepatic arterial resistance decreased, and the gastrointestinal resistance increased after the hemorrhage. Also the portal venous resistance was significantly increased. The hemorrhage resulted in hepatic glycogenolysis and peripheral glycolysis, but neither the splanchnic elimination of ethanol, consumption of oxygen nor hepatic dye elimination was decreased, and the hepatic redox level remained unaltered. The results indicate that although hemorrhage is accompanied by marked changes in hepatosplanchnic hemodynamics the intrahepatic distribution of blood flow is not subject to gross alterations.

Response of intrahepatic vasculature to isoproterenol and epinephrine influsions.

Response of hepatic arterial and intrahepatic portal venous vasculature to 10-min infusions of either isoproterenol or epinephrine was studied in 37 <i>in situ</i> dog liver preparations. Isoproterenol infusions at various dose rates (3.06–24.45 µg/min) were given by way of hepatic artery or portal vein. Hepatic arterial vasodilation, which was abolished by propranolol, was clearly evident while response of intrahepatic portal venous bed was incon sistent and not indicative of significant vasodilation. Arterial dilator response was attenuated later in the infusion period when isoproterenol was given at high dose rates. Femoral venous infusions of epinephrine (9.55 µg/min) resulted in a variable and slight hepatic arterial response while portal resistance was consistently increased. Following sotalol, epinephrine produced a marked increase in hepatic artery resistance in every case while intrahepatic portal venous resistance was increased to the same extent as before. It was concluded that both α-receptors (constrictors) and β-receptors (dilators) are present in canine hepatic arterial and mesenteric vessels while intrahepatic portal venous vasculature appears to possess few, if any, β-receptors.

Dilator responses of the canine hepatic vasculature.

Experiments were performed on 70 isolated, <i>in situ</i>, autoperfused canine liver preparations. Hepatic artery and portal venous flows were measured by means of an electromagnetic blood flowmeter. Effects of papaverine, dibenzyline, dibenamine and propranolol on hepatic artery and intra-hepatic portal venous vascular resistance were observed. Also the effects of these drugs on certain local vasomotor responses of the hepatic arterial bed (reactive hyperemia, autoregulation and reciprocity response to shunting of portal inflow) were also studied. Inhibition of vasodilator responses by these drugs was largely related to the amount of reduction in basal vascular tone which they produced.

Role of vasopressin and angiotensin in response of splanchnic resistance vessels to hemorrhage.

After hemorrhage, total hepatic flow decreases approximately in proportion to the decrease in cardiac output. This is associated with a slight increase in splanchnic vascular resistance (2,10,15). However, this response is the net result of marked vasoconstriction of the intestinal and splenic resistance vessels and vasodilatation of the hepatic arterial resistance vessels (2,12,14,15,18,20,29). Although these responses of the splanchnic resistance vessels to hemorrhage are well established, the mechanisms have not been investigated until recently.

Effect of temperature on the intra-hepatic vasculature.

In the isolated perfused liver of the dog, cooling produced vasoconstriction in the hepatic arterial bed and, particularly, in thee vascular bed of the portal vein. Raising the temperature to 40 degrees C dilated the portal venous bed but did not change hepatic arterial resistance. The portal venous bed is very sensitive to variations in temperature.

Augmentation of hepatic blood flow by acetylcholine

Acetylcholine was infused into the portal vein, hepatic artery, and the jugular vein of dogs at the rate of 0.1 mg per minute for one hour. Results of hepatic perfusion through the hepatic artery and portal vein were similar: a moderate fall in portal venous blood flow; nearly a twofold increase in hepatic arterial blood flow; and a net increase in total hepatic blood flow. Systemic hemodynamic parameters such as cardiac output, heart rate, blood pressure, and total peripheral resistance were not altered by regional hepatic infusion of this drug. Systemic infusion of acetylcholine through the jugular vein resulted in a 26 per cent increase in hepatic arterial blood flow and a 31 per cent fall in hepatic arterial resistance. These results were associated with similar systemic changes: a 21 per cent rise in cardiac output and a 28 per cent fall in total peripheral resistance. Because the marked local response to regional infusion of ACh was not associated with systemic hemodynamic alterations, this technic may have value in the treatment of patients who would benefit from increased hepatic arterial blood flow.

Adrenergic responses of the hepatic circulation.

ARTICLESAdrenergic responses of the hepatic circulationG Ross, and M KurraschG Ross, and M KurraschPublished Online:01 Jun 1969https://doi.org/10.1152/ajplegacy.1969.216.6.1380MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByAcid-Base Balance in Diabetic Ketoacidosis30 May 2008Negative impact of systemic catecholamine administration on hepatic blood perfusion after porcine liver transplantation21 January 2005 | Liver Transplantation, Vol. 11, No. 2Splanchnic Organ Blood Flow During Calcitonin Gene-Related Peptide-Induced Hypotension With or Without Propranolol in DogsAnesthesia & Analgesia, Vol. 90, No. 6Preserved arterial flow secures hepatic oxygenation during haemorrhage in the pig8 September 2004 | The Journal of Physiology, Vol. 516, No. 2Mechanisms Underlying the Neurogenic Relaxation in Dog Isolated Hepatic ArteriesJournal of Cardiovascular Pharmacology, Vol. 31, No. 3The role of the sympathetic nervous system in promoting liver cirrhosis induced by carbon tetrachloride, using the essential hypertensive animal (SHR)Journal of the Autonomic Nervous System, Vol. 37, No. 3Effects of various catecholamines on high-energy phosphates of rat liver and brain during hemorrhagic shock measured by31p-NMR spectroscopy1 September 1989 | Journal of Anesthesia, Vol. 3, No. 2Acute hepatic failure after open-heart surgery in childrenPediatric Cardiology, Vol. 8, No. 2Splanchnic and systemic hemodynamics in portal hypertensive rats during hemorrhage and blood volume restitutionGastroenterology, Vol. 90, No. 5The Comparative Effect of Administration of Substances Via the Hepatic Artery or Portal Vein on Hepatic Arterial Resistance, Liver Blood Volume and Hepatic Extraction in CatsHepatology, Vol. 4, No. 5Microcirculation of the Small IntestineFacial vein of the rabbit. Intracellularly recorded hyperpolarization of smooth muscle cells induced by beta-adrenergic receptor stimulation.Circulation Research, Vol. 52, No. 4Liver Blood FlowGastroenterology, Vol. 81, No. 2Acute Effects of Ethanol on Liver Blood Circulation in the Anesthetized DogAlcoholism: Clinical and Experimental Research, Vol. 4, No. 3Stimulation and blockade of cholinergic receptors in terminal liver microcirculation in rats.A Koo, and I Y Liang1 June 1979 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 236, No. 6THE ROLE OF β-ADRENOCEPTORS IN THE RESPONSES OF THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG TO PHENYLEPHRINE, ISOPRENALINE, NORADRENALINE AND ADRENALINE19 July 2012 | British Journal of Pharmacology, Vol. 60, No. 2The hepatic artery: Subservient to hepatic metabolism or guardian of normal hepatic clearance rates of humoral substancesGeneral Pharmacology: The Vascular System, Vol. 8, No. 2Effect of hepatic nerve stimulation on hepatic uptake of lidocaine in the catLife Sciences, Vol. 19, No. 3HEPATIC SINUSOIDAL RESPONSES TO INTRAPORTAL INJECTIONS OF PHENYLEPHRINE AND ISOPRENALINE IN THE RATClinical and Experimental Pharmacology and Physiology, Vol. 3, No. 4Hemodynamic effects of norepinephrine and isoprenaline in various regions of the canine splanchnic areaPfl�gers Archiv European Journal of Physiology, Vol. 365, No. 2-3The hepatic uptake of individual free fatty acids in sheep during noradrenaline infusionResearch in Veterinary Science, Vol. 18, No. 3Effects of acute administration of isoproterenol on the systemic and regional blood flow in the dogResuscitation, Vol. 3, No. 4Protective effects of propranolol on isoproterenol-induced myocardial infarction in arteriosclerotic and non-arteriosclerotic ratsAtherosclerosis, Vol. 18, No. 1Effect of Acute Isovolemic Anemia on Cardiac Output and Estimated Hepatic Blood Flow in the Conscious DogCirculation Research, Vol. 32, No. 4The Effect of Noradrenaline and Adrenaline on Hepatosplanchnic Hemodynamics, Functional Capacity of the Liver and Hepatic MetabolismActa Physiologica Scandinavica, Vol. 87, No. 3Regional circulatory effects of pancreatic glucagon20 July 2012 | British Journal of Pharmacology, Vol. 38, No. 4 More from this issue > Volume 216Issue 6June 1969Pages 1380-1385 Copyright & PermissionsCopyright © 1969 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1969.216.6.1380PubMed5786725History Published online 1 June 1969 Published in print 1 June 1969 Metrics

The effects of stimulation of the hepatic nerves, infusions of noradrenaline and occlusion of the carotid arteries on liver blood flow in the anaesthetized cat.

1. In anaesthetized cats, the hepatic artery, portal vein and inferior vena cava pressures and the hepatic artery and portal vein flows were recorded using pressure transducers and electro-magnetic flowmeters.2. The hepatic nerves were stimulated with maximal stimuli for periods of 2-5 min. The magnitude of the response varied with the frequency of stimulation over the range 1-10 impulses/sec. The resistance to flow increased in both the hepatic artery and the portal vein.3. In the hepatic artery, mean pressure remained virtually constant, while the flow showed an initial marked decrease followed by a return towards the control level. In the portal vein, the flow remained constant while portal pressure showed a maintained increase. These responses were unaffected by previous administration of atropine and propranolol, but were blocked by phenoxybenzamine.4. Infusions of noradrenaline into the hepatic artery produced changes similar to those following stimulation of the nerves. In contrast, when the hepatic arterial pressure was maintained constant, intravenous infusions of noradrenaline produced a maintained decrease in hepatic artery flow.5. The occurrence of autoregulation of the hepatic artery flow at arterial pressures above 80-100 mm Hg was confirmed.6. Occlusion of the carotid arteries caused a rise in arterial pressure with little change in hepatic artery flow, but when the hepatic artery pressure was maintained at the pre-occlusion level the flow showed an abrupt decrease, usually followed by a recovery towards the control level. This decrease was abolished by section of the hepatic nerves and removal of the adrenal glands.7. It is concluded that the increase in hepatic artery resistance during occlusion of the carotid arteries was dependent on the hepatic nerves, the adrenal medullary secretions and an intrinsic autoregulatory mechanism.

Arterial inflow into the mesenteric and hepatic vascular circuits during hemorrhagic shock.

Mesenteric artery and hepatic artery flows were studied in dogs during a standardized hemorrhagic shock procedure. Both flows decreased in response to hemorrhage, with development of greater vascular resistance in the hepatic artery circulation. Toward the end of the hypotensive period vascular resistance in the mesenteric artery often entered a declining phase, correlated with an increase in portal venous pressure, but hepatic artery resistance increased somewhat further. On transfusion, mesenteric artery flow increased rapidly, often exceeding the control values. Portal pressure doubled, and mesenteric resistance decreased to values less than control for about 30 minutes. This may represent a phase of pooling and trapping of blood in the capillaries and venules of the mesenteric circulation favored by reduced inflow resistance, and increased outflow resistance. This was followed by a phase of increased mesenteric resistance which often persisted until the demise of the animal, although it decreased in some animals during the terminal stage. Following transfusion, hepatic artery flow increased more gradually than mesenteric artery flow and reached a peak about 1 1/2 hours post-transfusion, at a time when flow in the mesenteric artery was markedly reduced and its resistance was maximal. The mechanism of this reciprocity of flow and resistance is discussed and its relevance to the interpretation of the hepatic artery flow changes in shock is considered.